ArticleScientific reports2015
Considerably Unfolded Transthyretin Monomers Preceed and Exchange with Dynamically Structured Amyloid Protofibrils.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- From Hummingbird to Elephant: Amyloid Formation in Natural Transthyretin Variants.bioRxiv : the preprint server for biology · 2026Article
- Transthyretin abnormalities in amyotrophic lateral sclerosis: High molecular weight species in cerebrospinal fluid and stromal deposits in choroid plexus.Journal of neuropathology and experimental neurology · 2025Article
- Mechanism of inhibition of acid-mediated transthyretin aggregation by designed peptides.The Journal of biological chemistry · 2025Article
- Differentiating the solution structures and stability of transthyretin tetramer complexed with tolcapone and tafamidis using SEC-SWAXS and NMR.Journal of applied crystallography · 2025Article
- A molecular basis for tetramer destabilization and aggregation of transthyretin Ala97Ser.Protein science : a publication of the Protein Society · 2023Article
- Role of conformational dynamics in pathogenic protein aggregation.Current opinion in chemical biology · 2023Review
- Transthyretin deposition alters cardiomyocyte sarcomeric architecture, calcium transients, and contractile force.Physiological reports · 2022Article
- Structural basis for transthyretin amyloid formation in vitreous body of the eye.Nature communications · 2021Article
- Transthyretin amyloid fibrils alter primary fibroblast structure, function, and inflammatory gene expression.American journal of physiology. Heart and circulatory physiology · 2021Article
- Transthyretin Misfolding, A Fatal Structural Pathogenesis Mechanism.International journal of molecular sciences · 2021Review
- Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Biophysical characterization and modulation of Transthyretin Ala97Ser.Annals of clinical and translational neurology · 2019Article
- Two distinct aggregation pathways in transthyretin misfolding and amyloid formation.Biochimica et biophysica acta. Proteins and proteomics · 2019Article
- A molecular mechanism for transthyretin amyloidogenesis.Nature communications · 2019Article
- Early Stage Alpha-Synuclein Amyloid Fibrils are Reservoirs of Membrane-Binding Species.Scientific reports · 2019Article
- Topological Analysis of Transthyretin Disassembly Mechanism: Surface-Induced Dissociation Reveals Hidden Reaction Pathways.Analytical chemistry · 2019Article
- Kinetic analysis of the multistep aggregation pathway of human transthyretin.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Amyloid fibril polymorphism: a challenge for molecular imaging and therapy.Journal of internal medicine · 2018Review
- Protein folding, misfolding and aggregation: The importance of two-electron stabilizing interactions.PloS one · 2017Article
- Solid-State NMR Studies Reveal Native-like β-Sheet Structures in Transthyretin Amyloid.Biochemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite numerous studies, a detailed description of the transthyretin (TTR) self-assembly mechanism and fibril structure in TTR amyloidoses remains unresolved. Here, using a combination of primarily small -angle X-ray scattering (SAXS) and hydrogen exchange mass spectrometry (HXMS) analysis, we describe an unexpectedly dynamic TTR protofibril structure which exchanges protomers with highly unfolded monomers in solution. The protofibrils only grow to an approximate final size of 2,900 kDa and a length of 70 nm and a comparative HXMS analysis of native and aggregated samples revealed a much higher average solvent exposure of TTR upon fibrillation. With SAXS, we reveal the continuous presence of a considerably unfolded TTR monomer throughout the fibrillation process, and show that a considerable fraction of the fibrillating protein remains in solution even at a late maturation state. Together, these data reveal that the fibrillar state interchanges with the solution state. Accordingly, we suggest that TTR fibrillation proceeds via addition of considerably unfolded monomers, and the continuous presence of amyloidogenic structures near the protofibril surface offers a plausible explanation for secondary nucleation. We argue that the presence of such dynamic structural equilibria must impact future therapeutic development strategies.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.